Representative Secretory Cells

Fig. 1. Schematic diagram SC, secretory cell BM, basement membrane Mon, monomer Dim, dimer representing the synthesis of the various forms of IgA by gut mucosal cells. From Tomasi (T5). Reproduced by courtesy of the publishers of (he New England Journal oj Medicine.

As mentioned above, the villi of the small intestine (Figure 1.2) house a dynamic, self-renewing population of the epithelial cells that includes absorptive cells (enterocytes), secretory cells, and endocrine cells. The thin lining (height 25 p,M height of the microvilli is 1.5 pM) of the columnar enterocytes is the only barrier between the intestinal lumen and the muscularis mucosa, which represents, in this context, the entire body interior. The entire epithelial lining of the intestine replaces itself every 3-5 d [128], It is the enterocyte and its neighboring cells where absorption processes occur and it will therefore be the focus of the mechanistic discussions below. 

In this volume a good deal of emphasis is placed on studies of dopamine receptors in pituitary. This emphasis seems well justified. The clear-cut effects of dopamine in suppressing prolactin secretion from anterior lobe mammotrophs, and the inhibitory effects on secretion of a-MSH and related secretory products from intermediate lobe are important models for dopamine receptor studies. In both cases new evidence was put forward to support the hypothesis that the actions of dopamine on the secretory cells are mediated by inhibition of adenylate cyclase. This is far easier to demonstrate in the intermediate lobe, where all cells appear to respond to dopamine, than in the anterior lobe, where the dopamine-sensitive cells probably represent only a small minority. 

Menthol is a well-known terpenoid from the essential oil of mint Mentha spp.) (15), and is described here as a representative of the different acyclic and cyclic plant monoterpenoids. Because of its pleasant odor, taste, and anesthetic and antimicrobial effects, (-)-menthol is an industrially important terpenoid and is produced commercially in large scale both from the essential oils of Mentha spp. and by asymmetric synthesis. The essential oil is produced in glandular trichomes, which are secretory cells that number in the thousands on Mentha leaves. The presence of these specialized cells, which easily can be separated physically from other cell types, has greatly facilitated studying (-)-menthol biosynthesis. 

Secretory cells often release vesicles spontaneously at a low rate whereas release rates increase when a stimulus arrives at the release site. For example, miniature synaptic potentials represent spontaneous release from the neuronal presynaptic terminal (Katz, 1966 Stevens, 1993). In contrast, sperm have only one secretory vesicle and, as discussed previously, cells that complete the acrosome reaction prior to egg contact are infertile. This problem may be circumvented, in part, by the fact that large numbers of sperm are produced by mammals, thereby minimizing the consequences of premature acrosome reactions in large populations. However,... 

Although it is possible to list all of the mammalian secretory cells and to note in some detail the biochemical nature of both precursor material and final secretory product, as well as to describe the intracellular pathway of secretory product formation, this would defeat the purpose of the current discourse. Rather, it will be more instructive to examine one secretory cell in detail and to compare it to several other representative cell types. From this analysis, one may derive an overview of the general mechanisms of secretion. For this purpose, I have chosen as a starting point the pancreatic exocrine cell because this cell has been one of the most thoroughly investigated, and its secretory pattern provides an ideal model on which to build broad concepts. 

The human pancreas secretes about 40—50 units of insulin daily, which represents about 15—20% of the hormone stored in the B cells. Insidin and the C-peptide (see Figure 42—12) are normally secreted in equimolar amounts. Stimuh such as glucose, which provokes insidin secretion, therefore trigger the processing of proinsidin to insidin as an essential part of the secretory response. 

Figure 46-6. Flow of membrane proteins from the endoplasmic reticulum (ER) to the cell surface. Horizontal arrows denote steps that have been proposed to be signal independent and thus represent bulkflow. The open vertical arrows in the boxes denote retention of proteins that are resident in the membranes of the organelle indicated. The open vertical arrows outside the boxes indicate signal-mediated transport to lysosomes and secretory storage granules. (Reproduced, with permission, from Pfeffer SR, Rothman JE Biosynthetic protein transport and sorting by the endoplasmic reticulum and Golgi. Annu Rev Biochem 1987 56 829.)...

The coat mucins are thought to be secreted from two major glands in the larval body the oesophageal and secretory glands. The latter, previously termed the excretory cell, is directly connected to the cuticle by a duct opening at the secretory pore (Nichols, 1956). It is not certain whether the panel of secreted mucins are all represented in the coat, or whether there are important differences between the two compartments. 

The most widely studied therapeutic proteins produced in plants include monoclonal antibodies for passive immunotherapy and antigens for use as oral vaccines [40]. Antibodies against dental caries, rheumatoid arthritis, cholera, E. coli diarrhea, malaria, certain cancers, Norwalk virus, HIV, rhinovirus, influenza, hepatitis B virus and herpes simplex virus have been produced in transgenic plants. However, the anti-Streptococcus mutans secretory antibody for the prevention of dental caries is the only plant-derived antibody currently in Phase II clinical trials [40]. Until recently, most antibodies were expressed in tobacco, potato, alfalfa, soybean, rice and wheat [9], It has been estimated that for every 170 tons of harvested tobacco, 100 tons represents harvested leaves. A single hectare could thus yield 50 kg of secretory IgA [3, 41]. Furthermore, it has been estimated that the cost of antibody production in plants is half that in transgenic animals and 20 times lower than in mammalian cell cul-... 

The major antibody isotype in external secretions is sIgA, and the total amount of IgA synthesized is twice the amount of IgG produced daily in humans. IgA cells represent up to 80% of the entire mucosal lymphoid cell population. sIgA in mucosal secretions results from polymeric IgA transported across mucosal epithelium via binding to the pIgRreceptor (also known as the secretory component). The receptor is eventually cleaved and results in an IgAipIgR complex, referred to as sIgA (Figure 7.2) (Rojas and Apodaca, 2002). 

---